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1.
World J Cardiol ; 16(8): 491-495, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39221193

ABSTRACT

BACKGROUND: Antiphospholipid syndrome (APS) is a chronic autoimmune disease characterized by venous or arterial thrombosis, pregnancy morbidity and a variety of other autoimmune and inflammatory complications. Here, we report a case of APS associated with multiple coronary thromboses. CASE SUMMARY: The patient, a 28-year-old male, suffered from recurrent coronary thromboses over a period of 31 months. Despite undergoing interventional coronary procedures, thrombolytic therapy, and anticoagulation treatment, the condition persisted intermittently. An extensive search for underlying thrombogenic factors revealed a diagnosis of APS. Accurate adjustment of the medication regimen led to the absence of further acute coronary syndrome (ACS) episodes during the subsequent 20-month follow-up. Although the patient occasionally experiences chest tightness, no further symptoms of distress have been reported. CONCLUSION: APS can manifest as ACS. Screening for rheumatologic and immunological conditions is essential when encountering patients with multiple coronary thromboses. Treatment strategy should include symptomatic relief and a targeted and aggressive approach to address the underlying pathophysiology.

2.
Lupus ; 33(12): 1383-1388, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39244660

ABSTRACT

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is often associated with antiphospholipid syndrome (APS), which manifests as recurrent thrombotic events or obstetric complications in presence of antiphospholipid antibodies. Hereby we present a case of a child who presented with low grade fever, superficial thrombophlebitis with mucosal bleeding and was diagnosed as Lupus Anticoagulant Hypoprothrombonemia Syndrome (LAHS). CASE: A 7-year-old girl was hositalized with complaints of fever and spontaneous bleeding from gums and epistaxis. On examination, she had multiple small tender nodular lesions with greenish hue of overlying skin suggesting superficial thrombophlebitis and mild non-tender hepatosplenomegaly. Her coagulogram revealed normal platelet counts and deranged PT and APTT. ESR and CRP were raised. Serology for viral infections, blood and urine cultures were negative. Patient had persistent coagulopathy, mucosal bleeding and low-grade fever despite supportive treatment. She was tested for anti-nuclear antibodies (ANA) in view of suspicion of autoimmune process. ANA was positive in high titer with speckled pattern on indirect immunofluorescence. Mixing studies showed correction of PT and non-correction of APTT. PT based factors were normal except for prothrombin (FII) which was low and remained low despite dilution. APTT based factors (FVIII and FIX) were low but corrected on dilution. This was suggestive of prothrombin deficiency and a presence of a nonspecific inhibitor of APTT pathway (likely lupus anticoagulant). Presence of antiprothrombin antibodies established the diagnosis of LAHS. ENA profile was positive for SmD1, Ro60 and Ku. Complement levels were low. Direct Coomb's test was positive but there was no evidence of hemolysis. Lupus anticoagulant by DRVVT and anti-cardiolipin antibodies by ELISA were positive. Patient was diagnosed as Systemic Lupus Erythematosus with Lupus Anticoagulant Hypoprothrombinemia Syndrome. She was treated with IV methylprednisolone. Patient showed significant improvement in form of resolution of fever, mucosal bleeding, correction of deranged INR and reversal of hypocomplementemia. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering doses of prednisolone. On follow up, child was doing well and her prothrombin time and complement levels had normalized. Low dose aspirin was aspirin was added for thromboprophylaxis.


Subject(s)
Antiphospholipid Syndrome , Lupus Coagulation Inhibitor , Lupus Erythematosus, Systemic , Humans , Female , Lupus Coagulation Inhibitor/blood , Child , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/blood , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/drug therapy , Hypoprothrombinemias/diagnosis , Antibodies, Antinuclear/blood , Hemorrhage/etiology
3.
Res Pract Thromb Haemost ; 8(6): 102536, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39290988

ABSTRACT

Background: Testing for lupus anticoagulant (LA) is not recommended in case of inflammation as C-reactive protein (CRP) can interfere in vitro with the phospholipids present in the activated partial thromboplastin time test used to detect an LA. However, the potential interference of an acute phase protein (ie, CRP) in LA testing using the dilute Russell's viper venom (DRVV) test is poorly studied. Objectives: To study the effect of inflammation, as evidenced by increased CRP levels, on DRVV tests. Methods: First, a retrospective analysis (2013-2023) was performed: data on all LA workups were retrieved, and the association between CRP levels and DRVV screen, mix, and confirm clotting times was studied. Second, data on DRVV panels and CRP levels were extracted from 2 prospective studies involving intensive care unit patients to study the association between both variables. Third, CRP was added to normal pooled plasma at 6 relevant concentrations (up to 416 mg/L) to study the association between CRP itself and DRVV coagulation times. Results: In the retrospective analysis, DRVV screen and confirm clotting times significantly increased as CRP increased (increase of 0.11 seconds and 0.03 seconds per 1 mg/L increase of CRP level, respectively). In the prospective analysis, only DRVV screen was prolonged with high CRP levels (increase of 0.06 seconds for a 1 mg/L increase in CRP level); DRVV screen/confirm ratio was also increased with high CRP levels. In vitro, the addition of CRP did not significantly increase any DRVV clotting times. Conclusion: LA testing should be performed with much caution in the presence of inflammation as it may be associated with prolongation of both activated partial thromboplastin time and DRVV clotting times.

4.
Lab Med ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39213365

ABSTRACT

BACKGROUND: Activated partial thromboplastin time (APTT) is susceptible to reagent composition. This study aimed to investigate a large number of specimens and determine the cause of discrepancies. METHOD: This study included 18,994 subjects who underwent coagulation tests at our hospital from May 2020 to December 2020. Measuring reagents included HemosIL SynthASil APTT (APTT-SS, Instrumentation Laboratory) and Coagpia APTT-N (APTT-N, Sekisui Medical). RESULTS: A total of 451 patients demonstrated APTT-N of >39 seconds and an APTT-N/SS ratio of >1.3. A C-reactive protein (CRP) level of ≥1.4 mg/L demonstrated a significant positive correlation, with a higher APTT-N/SS indicating higher CRP levels. All 28 subjects receiving no anticoagulants and who had remaining specimens underwent a cross-mixing test (CMT). Of them, 17 were suspected for lupus anticoagulant (LA) by both the waveform shape and the index of circulating anticoagulant (ICA) value, 6 by the ICA value, and 5 were difficult to determine. CONCLUSION: This study revealed that the APTT-N prolongation correlated with CRP degree and the transient involvement of LA in CMT results due to CRP. This study indicated various reactivities depending on the assay reagents used. Further testing is warranted if LA is suspected, considering the patient's background.

5.
Med Clin (Barc) ; 163 Suppl 1: S1-S3, 2024 08.
Article in English, Spanish | MEDLINE | ID: mdl-39174147

ABSTRACT

In the 40 years since the original detailed description of antiphospholipid syndrome (APS), the condition has come to be regarded as one of the most common autoimmune diseases. The impact of the description has been enormous - for example, the recognition that some individuals with connective tissue diseases require anticoagulation rather than corticosteroids or anti-inflammatory treatment has bought about fundamental change in medical practice. In obstetrics, APS is now regarded as the most important prothrombotic cause of recurrent pregnancy loss - with pregnancy success improving from below 20% to current live birth rate over 80%. In neurology, APS may be associated with up to 20% of strokes in people under 40 - a striking figure not least in terms of medical economics, let alone in potentially preventable suffering. In vascular medicine, APS links immunology with thrombosis and vascular disease and may well provide insights into immunological factors in the pathogenesis of atherosclerosis.


Subject(s)
Antiphospholipid Syndrome , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Humans , Pregnancy , Female , History, 20th Century , Pregnancy Complications
6.
Med Clin (Barc) ; 163 Suppl 1: S22-S30, 2024 08.
Article in English, Spanish | MEDLINE | ID: mdl-39174150

ABSTRACT

Thrombotic manifestations, mainly venous thromboembolism (VTE) and stroke, are the most common and potentially life-threatening presentations of antiphospholipid syndrome (APS). The management of APS requires the assessment of the antiphospholipid antibodies (aPL) profile, of concurrent systemic lupus erythematosus or other systemic autoimmune diseases and the presence of risk factors for cardiovascular disease and bleeding. Anticoagulation with vitamin K antagonists (VKA) remains the cornerstone of therapy for thrombotic APS. As platelets play a central role in APS, low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers, and also plays a role as combination therapy with VKAs in arterial thrombosis. Treatment with direct oral anticoagulants (DOACs) could be considered in certain low-risk situations, although they are not recommended in patients with arterial thrombosis or triple positive aPL. Adjuvant therapies such as hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding. In this article, we review the evidence and the recommendations of the guidelines for the treatment of APS, and provide a critical and practical approach of its management from our clinical perspective.


Subject(s)
Anticoagulants , Antiphospholipid Syndrome , Practice Guidelines as Topic , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/drug therapy , Humans , Anticoagulants/therapeutic use , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Antibodies, Antiphospholipid/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Risk Factors
7.
Med Clin (Barc) ; 163 Suppl 1: S14-S21, 2024 08.
Article in English, Spanish | MEDLINE | ID: mdl-39174149

ABSTRACT

Antiphospholipid syndrome (APS) is the most frequent acquired thrombophilia of autoimmune basis. Pregnancy complications of APS may include recurrent miscarriage, and placental dysfunction presenting as fetal death, prematurity, intrauterine growth restriction and preeclampsia. For the management of obstetric APS, a coordinated medical-obstetric management is essential, and this should start for a preconceptional visit in order to estimate the individual risk for complications, adjust therapies and establish the indications for preconceptional and first-trimester therapy. The basis of APS therapy during pregnancy is low-dose aspirin, combined in certain clinical scenarios with low-molecular weight heparin. Induction of delivery should not be routinely indicated in the absence of maternal and/or fetal complications. Postpartum management should be warranted.


Subject(s)
Antiphospholipid Syndrome , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Humans , Pregnancy , Female , Aspirin/therapeutic use , Pregnancy Complications/therapy , Pregnancy Complications/diagnosis , Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Pregnancy Complications, Hematologic/diagnosis , Pregnancy Complications, Hematologic/therapy
8.
Med Clin (Barc) ; 163 Suppl 1: S4-S9, 2024 08.
Article in English, Spanish | MEDLINE | ID: mdl-39174152

ABSTRACT

Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins and are associated with several clinical settings, and most notably define the antiphospholipid syndrome (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for APS, which are also applied as diagnostic markers in medical practice. This review provides an overview of the available laboratory tests currently for measuring aPL and discusses their clinical implications.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Antibodies, Antiphospholipid/blood , Pregnancy , Female , Lupus Coagulation Inhibitor/blood , Biomarkers/blood
9.
Lupus ; 33(12): 1373-1378, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39152759

ABSTRACT

INTRODUCTION: The gut microbiome is recognized as a factor that could potentially contribute to the persistent antibodies of antiphospholipid syndrome (APS). Gut microbial interventions can both induce and mitigate APS in mice. In human APS patients, anti-beta-2-glycoprotein I (ß2GP-1) titers correlate with antibody titers against a gut commensal protein homologous to ß2GP-1. AIM: To  investigate the effect of the intestinal microenvironment on human APS. Methods We cross-sectionally compared intestinal microbiota composition quantified by shotgun sequencing; fecal short chain fatty acids (SCFAs), bacterial metabolites known to affect autoimmune processes; and fecal calprotectin, an intestinal inflammatory marker, in APS patients and healthy controls. RESULTS: Neither alpha nor beta diversity of the gut microbiota differed between APS patients (n = 15) and controls (n = 16) and no taxa were differentially abundant. Moreover, fecal SCFAs and fecal calprotectin, did not differ between the groups. CONCLUSION: Gut microbiome effects on the APS phenotype are likely not driven by bacterial overabundance, SCFA production or intestinal inflammation.


Subject(s)
Antiphospholipid Syndrome , Fatty Acids, Volatile , Feces , Gastrointestinal Microbiome , Leukocyte L1 Antigen Complex , Gastrointestinal Microbiome/immunology , Antiphospholipid Syndrome/immunology , Humans , Female , Feces/microbiology , Middle Aged , Male , Adult , Cross-Sectional Studies , Case-Control Studies , Leukocyte L1 Antigen Complex/analysis , Leukocyte L1 Antigen Complex/metabolism , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/analysis , beta 2-Glycoprotein I/immunology , Aged , Intestines/immunology , Intestines/microbiology
10.
Lupus ; 33(11): 1220-1226, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39154283

ABSTRACT

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is an autoimmune disease having a variety of clinical symptoms because of multiple organs being affected at once or progressively over time. Cardiovascular system (CVS) involvement is the third most frequent cause of death in SLE, among other factors. The prognosis can be determined by looking at QT interval measurements, which have shown an elevated risk of mortality from cardiovascular causes. METHODS: A case-control study was conducted on 80 patients (40 SLE patients and 40 controls) for a duration of 16 months. SLE patients and controls were identified from the general medicine and rheumatology outpatient department (OPD) based on the inclusion criteria. A thorough clinical examination was performed after obtaining a detailed clinical history. Baseline blood tests were then performed on the SLE patients and ECG was taken from both cases and controls. The serum uric acid level was measured using an automated analyzer, and the ESR was computed using Westergren's Method. The corrected QT interval (QTc) was estimated using Bazett's method. All the collected data were compared and analyzed using IBM SPSS Statistics version 23.0. RESULTS: The majority of age distribution among SLE patients and controls was 21-25 years (37.5%) (Mean - 15.7 ± 14.9 years). Duration of SLE was predominantly reported between 1 and 12 months (62.5%). Very high (40%) and high (40%) lupus disease activity was recorded in the majority as per the SELENA-SLEDAI score. There was a significant difference between QTc values among SLE patients and controls (t- 8.117) (p-.0005). Upon correlating SLEDAI with the QTc, QTd, ESR, and Uric acid parameters among the SLE patients, ESR parameters were found to be moderately correlated (r-0.460) with the SLEDAI which was statistically significant (p- .003). CONCLUSION: QTc interval and ESR values can be a simple and potential method for early detection of cardiac involvement in SLE patients with active disease activity. This will not only facilitate early diagnosis of disease activity, but it will also provide an affordable and accessible avenue for low and middle-income countries to decrease the SLE burden.


Subject(s)
Blood Sedimentation , Electrocardiography , Lupus Erythematosus, Systemic , Uric Acid , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/physiopathology , Uric Acid/blood , Adult , Female , Case-Control Studies , Male , Young Adult , Adolescent , Middle Aged
11.
Cureus ; 16(7): e63992, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39109126

ABSTRACT

Evans syndrome (ES), characterized by autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP), often poses diagnostic challenges due to its varied etiology and clinical presentation. We present a case of secondary ES in a 41-year-old male with a history of AIHA and ITP, who presented with lower extremity erythema, warmth, and sensation of chest pressure. Initial laboratory investigations revealed thrombocytopenia, mild anemia, and a prolonged activated partial thromboplastin time (aPTT), prompting further evaluation. Subsequent testing revealed positive lupus anticoagulant (LA), anti-cardiolipin antibodies, and anti-beta-2-glycoprotein 1 antibodies, along with lower extremity deep vein thrombosis (DVT) and bilateral pulmonary embolism (PE). Treatment with therapeutic anticoagulation led to clinical improvement, highlighting the importance of recognizing hypercoagulable states in ES patients. This case underscores the significance of comprehensive differential diagnosis and timely intervention in optimizing outcomes for patients with ES.

12.
PeerJ ; 12: e17617, 2024.
Article in English | MEDLINE | ID: mdl-38948200

ABSTRACT

Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-ß2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti-ß 2GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.


Subject(s)
Antiphospholipid Syndrome , Atrial Fibrillation , Humans , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Retrospective Studies , Female , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Male , Middle Aged , Case-Control Studies , Risk Factors , Antibodies, Anticardiolipin/blood , Adult , Aged , beta 2-Glycoprotein I/immunology , China/epidemiology
13.
Article in English | MEDLINE | ID: mdl-39041283

ABSTRACT

OBJECTIVE: The purpose of this study was to determine the etiologies of recurrent miscarriage in our hospital and whether its diagnostic approach followed the recommendations of the American Society of Reproductive Medicine (ASRM) guidelines published in 2012 and the National Institute for Health and Care Excellence (NICE) guidelines published in 2011. METHODS: This was a retrospective study. The medical records of 158 patients diagnosed with recurrent miscarriage between 2013 and 2018 at Santander University Hospital were reviewed. The Institutional Review Board of HUS approved the study in May 2020. RESULTS: The most common etiologies identified were protein S deficiency, thrombophilia, and cervical insufficiency, with incidence rates of 25.9%, 10.7%, and 3.8%, respectively. Moreover, the most frequently requested diagnostic tests were for protein S, protein C, and anti-phospholipid IgG. Abnormal results for protein S were obtained in 49% of the patients, whereas lupus anticoagulant was abnormal in 12.8%, and Factor V Leiden gene mutations in 8.5% of the patients. Three substantial deviations from the recommended diagnostic approach for recurrent miscarriage by international guidelines were identified in our population: the lack of request for cytogenetic analysis of pregnancy tissue, request for cytogenetic analysis for the parents in only 0.6% of the study sample, and the request for imaging tests to assess uterine anatomy in only 6.3% of the studied population. Both the ASRM and NICE guidelines were only partially followed with a combined adherence rate of 66.5%. CONCLUSION: The diagnostic approach for recurrent miscarriage poses important clinical challenges when compared to the recommendations of international guidelines. Therefore, the development of a local recurrent miscarriage assessment protocol is proposed in our institution.

14.
Ceska Gynekol ; 89(3): 237-244, 2024.
Article in English | MEDLINE | ID: mdl-38969520

ABSTRACT

AIM AND METHODOLOGY: To provide a comprehensive review on new findings and current recommendations regarding antiphospholipid antibodies with particular emphasis on clinical impact on gestation. CONCLUSION: Antiphospholipid antibodies are an important risk factor for the development of a series of pregnancy-related complications. Early diagnosis and appropriate therapy can reduce the incidence of pregnancy loss and pregnancy-related complications.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Pregnancy Complications , Humans , Pregnancy , Female , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/complications , Pregnancy Complications/immunology
15.
Cureus ; 16(6): e61713, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975541

ABSTRACT

The antiphospholipid syndrome (APS) manifests through venous or arterial thrombosis, with or without pregnancy complication alongside the continuous presence of antiphospholipid antibodies (aPL). APS classification relies on three aPL subtypes: anticardiolipin (aCL), anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulants (LA) antibodies. Given that thrombosis and pregnancy issues are not unique to APS, the precise and reliable identification of aPL forms the basis for diagnosis. Semi-quantitative solid-phase assays identify two antibodies, aCL and anti-ß2GPI, while LA detection occurs through various phospholipid-dependent coagulation assays that are based on antibody behaviour. LA, specifically, is conclusively associated with thrombosis, prompting discussions around the serological criteria for APS. Despite advancements in LA detection, the standardisation of all aPL detection assays remains imperative. The combined presence of aCL and anti-ß2GPI with thrombosis inconsistently triggers concern. Initial presentations by APS patients commonly exhibit a heightened risk of stroke, miscarriages in the later stages of pregnancy, positive results of LA tests, and widespread thrombosis across multiple organs, often leading to adverse outcomes. Correctly diagnosing this condition is pivotal to avoid unnecessary long-term secondary thromboprophylaxis.

16.
Pediatr Int ; 66(1): e15773, 2024.
Article in English | MEDLINE | ID: mdl-38863279

ABSTRACT

BACKGROUND: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disease caused by acquired factor II (FII) deficiency and lupus anticoagulant. Patients with LAHPS typically present with thrombosis and bleeding. However, little information is available on the evaluation of coagulation potential in patients with LAHPS. We examined global coagulation potentials in patients with LAHPS during the clinical course in this study. METHODS: Coagulation potentials in two pediatric patients with LAHPS were assessed by measuring clotting time (CT) and clot formation time using Ca2+-triggered rotational thromboelastometry (ROTEM), CT and maximum coagulation velocity using clot waveform analysis (CWA), and lag time and peak thrombin using the thrombin generation assay (TGA). The day of admission was defined as day 0. RESULTS: In case 1, the bleeding symptoms disappeared by day 5. However, the TGA and CWA results were markedly lower than normal, although FII activity (FII:C) returned to within the normal range by day 14. In contrast, ROTEM revealed a recovery to near-normal levels (day 14). All coagulation parameters (day 80) were within normal ranges. In case 2, coagulation potential was severely depressed until day 12, although FII:C returned to normal levels. Bleeding symptoms disappeared on day 19, and the ROTEM data revealed that the parameters were close to the normal range. The coagulation parameters in all assays were normalized on day 75. CONCLUSIONS: Recovery of coagulation potential in patients with LAHPS was slower than the recovery of FII:C. Moreover, ROTEM appeared to be clinically useful for assessing coagulation potential in patients with LAHPS.


Subject(s)
Hypoprothrombinemias , Lupus Coagulation Inhibitor , Thrombelastography , Humans , Hypoprothrombinemias/blood , Hypoprothrombinemias/diagnosis , Lupus Coagulation Inhibitor/blood , Female , Thrombelastography/methods , Male , Child , Blood Coagulation Tests/methods , Blood Coagulation/physiology , Child, Preschool , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis
17.
J Thromb Haemost ; 22(10): 2797-2809, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38944242

ABSTRACT

BACKGROUND: Antiphospholipid antibodies (aPL), including lupus anticoagulant, antibodies against ß2 glycoprotein I (anti-ß2GPI), and anticardiolipin (aCL) antibodies are associated with ischemic stroke (IS). Their prevalence and clinical relevance in atrial fibrillation (AF) remain unclear. OBJECTIVES: To assess whether aPL are associated with increased risk of IS in AF patients despite anticoagulation. METHODS: We conducted a post hoc analysis of aPL using blood samples from 243 consecutive AF patients enrolled in a cohort study. Markers of a prothrombotic state, including endogenous thrombin potential, fibrin clot permeability, and lysis time, were measured at baseline. During a median follow-up of 52 months, IS/transient ischemic attack and major bleeding were recorded. RESULTS: We observed aPL at a moderate or high titer in 51 (21%) patients, including 17 (7%) with anti-ß2GPI, 19 (7.8%) with aCL antibodies, and 37 (15.2%) with lupus anticoagulant. aPL-positive patients were more likely to have prior stroke (P = .01) and be active smokers (P = .03), along with increased endogenous thrombin potential (P = .02), without any changes in fibrin clot properties. Anti-ß2GPI (hazard ratio, 4.38; 95% CI, 1.58-12.19) and aCL (hazard ratio, 4.70; 95% CI, 1.80-12.30) at a moderate or high titer were associated with IS during follow-up (n = 20; 1.9% per year). There were 23 major bleedings (2.1% per year) and 20 deaths (1.9% per year), which were not associated with aPLs. CONCLUSION: Our study showed a relatively high prevalence of aPL positivity in AF patients, which was linked to an increased risk of IS/transient ischemic attack. This suggests that screening for aPL might help optimize anticoagulant therapy in such patients.


Subject(s)
Antibodies, Antiphospholipid , Atrial Fibrillation , Ischemic Stroke , Lupus Coagulation Inhibitor , Humans , Female , Male , Aged , Antibodies, Antiphospholipid/blood , Ischemic Stroke/blood , Ischemic Stroke/immunology , Ischemic Stroke/epidemiology , Ischemic Stroke/diagnosis , Middle Aged , Risk Factors , Atrial Fibrillation/blood , Atrial Fibrillation/immunology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/complications , Lupus Coagulation Inhibitor/blood , Biomarkers/blood , beta 2-Glycoprotein I/immunology , Hemorrhage/blood , Risk Assessment , Antibodies, Anticardiolipin/blood , Ischemic Attack, Transient/blood , Ischemic Attack, Transient/immunology , Aged, 80 and over , Anticoagulants/therapeutic use , Time Factors , Prospective Studies , Blood Coagulation
18.
Biochem Med (Zagreb) ; 34(2): 020504, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38882589

ABSTRACT

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-ß2-glycoprotein I (aß2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aß2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/immunology , Antibodies, Antiphospholipid/blood , Female , Pregnancy , Antibodies, Anticardiolipin/blood , Lupus Coagulation Inhibitor/blood , Enzyme-Linked Immunosorbent Assay
19.
J Clin Med ; 13(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38892776

ABSTRACT

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-ß2-glycoprotein I (ß2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.

20.
Am J Clin Pathol ; 162(4): 379-391, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-38741421

ABSTRACT

OBJECTIVES: To evaluate the utility of the dilute prothrombin time (DPT) in diagnosing antiphospholipid syndrome (APS), alone and when paired with the dilute Russell viper venom time (DRVVT). METHODS: Dilute prothrombin time and DRVVT testing was performed on plasma samples spiked with apixaban or rivaroxaban, or depleted of vitamin K-dependent clotting factors. A retrospective analysis of all functional APS testing results over a 44-month period at the University of Chicago Medical Center was performed. RESULTS: In spiking studies, the screening clotting time in the DPT (DPTS) is more sensitive to deficiency of vitamin K-dependent factors than is the screening clotting time in the DRVVT (DRVVTS). The converse is true for factor Xa direct oral anticoagulant (DOAC)-spiked plasma. In a 44-month retrospective analysis, only 2.6% of clinical APS panels showed isolated positivity in the DPT-based system. Comparing the DPT-based system with the DRVVT-based system showed utility in identifying false-positive DRVVT results due to anticoagulation. A DRVVTS/DPTS ratio of 0.785 or lower predicted an international normalized ratio of 1.5 or higher (sensitivity, 86.3%; specificity, 60.4%; likelihood ratio, 2.18). Conversely, a DRVVTS/DPTS ratio of 1.165 or higher was the optimal cutoff for predicting the identification of factor Xa DOAC (sensitivity, 61.8%; specificity, 77.8%; likelihood ratio, 2.78). Within the data set that had full DRVVT and DPT results, parameters were identified that could further improve identification of samples with anticoagulation interference. CONCLUSIONS: Dilute prothrombin time lupus anticoagulant assay is rarely the sole laboratory functional evidence for APS, but when combined with the DRVVT, the DPT can serve as an effective screen for common anticoagulant interference.


Subject(s)
Antiphospholipid Syndrome , Prothrombin Time , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/blood , Humans , Retrospective Studies , Sensitivity and Specificity
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